title: Preadolescent drd1-EGFP mice exhibit cocaine-induced behavioral sensitization.
abstract: In adult mice, repeated cocaine administration induces behavioral sensitization measured as increased horizontal locomotor activity. Cocaine-induced locomotor sensitization has been well characterized in adult mice. In adult animals, the D1 dopamine receptor is important for mediating effects of cocaine. The effect of cocaine on D1 receptor expression and function in preadolescent animals is less understood. The recently described drd1-enhanced green fluorescent protein (drd1-EGFP) reporter mouse is a useful model for performing such mechanistic studies; however, preadolescent drd1-EGFP mice have not been characterized previously. Here we studied cocaine-induced locomotor sensitization in preadolescent drd1-EGFP reporter mice. We administered 15mg/kg cocaine three times daily at 1h intervals for seven consecutive days beginning on postnatal day 23 to drd1-EGFP reporter mice and the commonly used C57BL/6 mice. Under this regimen, preadolescent mice of both strains exhibited cocaine-induced locomotor sensitization; however, by day 7 the cocaine-induced locomotor activity in the drd1-EGFP mice was maintained for a longer duration compared to the C57BL/6 mice. The preadolescent drd1-EGFP mice also exhibited elevated basal locomotor activity in a novel environment and had higher D1 and D2 dopamine receptor mRNA levels in the caudate nucleus compared to the C57BL/6 mice. The cocaine-induced locomotor sensitization was not retained when the drd1-EGFP mice were maintained cocaine-free for two weeks suggesting that in preadolescent drd1-EGFP mice the cocaine-induced changes do not persist.
authors.affiliation: Department of Pharmacology and Physiology, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Krishna E
authors.initials: KE
authors.lastname: Tobón
authors.affiliation: Department of Pharmacology and Physiology, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA. Electronic address: kuzhikev@njms.rutgers.edu.
authors.forename: Eldo V
authors.initials: EV
authors.lastname: Kuzhikandathil
mesh_terms: D000367:Age Factors; D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D003042:Cocaine
keywords: ANOVA; Behavioral sensitization; Binge cocaine; Dopamine receptors; EGFP; Locomotor activity; PAS; Preadolescent; RT-PCR; Withdrawal; analysis of variance; enhanced green fluorescent protein; photobeam activity system; reverse transcriptase-polymerase chain reaction